靶向毒素DT-VEGF的构建、表达与活性分析  

Construction, Expression and Bioactivity Characterization of Targeting Toxin DT-VEGF

作　　者：柴映爽[1] 程新[1] 姚立红[1] 陈爱珺[1] 喻宏[1] 严馨蕊[1] 贾润清[1] 黄国锦[1] 张智清[1] 

机构地区：[1]中国疾病预防控制中心病毒病预防控制所病毒基因工程国家重点实验室

出　　处：《生物工程学报》2004年第2期192-196,共5页Chinese Journal of Biotechnology

摘　　要：肿瘤的快速生长依赖于新生血管的形成。血管内皮生长因子 (VEGF)是血管发生和形成过程中的主要介质 ,其特异性受体在正常组织和肿瘤组织的表达率存在数个数量级的差异 ,因此可以将毒素分子转运至增生的肿瘤上皮组织中抑制肿瘤血管增生 ,从而抑制肿瘤的生长。将白喉毒素的前 3 89个氨基酸基因片段与VEGF165通过一短肽相连构建为融合蛋白基因 ,在大肠杆菌中表达 ,获得纯化蛋白。实验证实该融合蛋白对血管内皮细胞有特异性杀伤作用 。Tumor rapid growth depends on neovascularization. Vascular endothelial growth factor, the main mediator during the occurrence and formation of vascular ization, has specific receptors whose expression rate shows difference of orders of magnitude between tumor and the normal tissue, so it can be used to transpor t toxin molecules to the proliferative tumor endothelial and kill cancer cells. In our experiment, we constructed fusion protein DT-VEGF by linking diphtheria toxins forward 389 amino acidss gene and VEGF165 via a linker. DT-VEGF is exp ressed in E.coli and purified. Our experiment proves in can kill vascular en dothelial cells specifically, and the inhibition of neovascularization of chicke n chorionic membrane is also confirmed.

关 键 词：靶向毒素 DT-VEGF 血管内皮生长因子 白喉毒素 融合蛋白 基因 表达 活性 肿瘤 

分 类 号：R73-3[医药卫生—肿瘤]